We propose to investigate a range of questions regarding the transformation of cells to malignancy, the role of mutagens and anti-mutagens in this process, and the distinguishing molecular events associated with neoplasia. Efforts of the individual investigators will interdigitate with respect to research plans, joint experiments, literature review, and sharing of facilities used for these studies. The specific problems to be investigated are the following: I. Maintenance of chromosome stability: structure and function of the telomere. II. Quantitative assays of mutagenic and carcinogenic susceptibility of human cells. III. Protection of cells against neoplastic transformation using agents that alter DNA repair processes. IV. Studies of transformation-sensitive cell surface proteins. V. The role of platelet wound hormone in transformation, cellular quiescence, and epithelial cell growth. The methodologies to be applied include tissue culture, cell implantation in athymic (nude) mice, recombinant DNA, biochemical methods for studies of DNA and protein, autoradiography and other radioactive tracer methods, and isolation and characterization of mutated and transformed cells.